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High metabolic risk burden increases HCC risk in HBV patients

medwireNews: A high burden of metabolic risk factors significantly increases the risk for hepatocellular carcinoma (HCC) among men with hepatitis B virus (HBV) infection, particularly those who smoke, researchers from Taiwan report.

These findings indicate that “[nonalcoholic fatty liver disease]/metabolic syndrome may play a non-negligible role in determining risk of HBV-related HCC,” Ming-Whei Yu (National Taiwan University, Taipei) and study co-authors remark.

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They found that, during a median follow-up period of 19.2 years, 158 of 1690 men (median age 48.4 years, median body mass index 23.7 kg/m2) with HBV developed HCC and 126 died from liver-related diseases. This compared with five HCC cases and four liver-related deaths among 1289 men without HBV or hepatitis C virus (HCV) infection in the same age range (40–65 years) from the same civil servant cohort.

As reported in Gastroenterology, the cumulative incidence of HCC and liver-related death increased significantly with increasing metabolic risk burden (p for trend=0.0468 and 0.0068, respectively).

For example, the 10-year cumulative incidence of HCC increased from 4.8% in HBV carriers with no metabolic risk factors to 13.6% in those with three or more risk factors, among whom 92.5% were obese and 45.3% had diabetes.

After adjusting for age, smoking status, alcohol consumption, and family history of HCC, the hazard ratios (HRs) for HCC and liver-related death with three or more versus no metabolic risk factors were 2.32 and 2.72, respectively.

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The results did not change when the 6.2% of HBV carriers who were also positive for anti-HCV antibodies were excluded from the analysis or when the findings were further adjusted for history of cirrhosis.

However, the researchers found that there was a strong interaction between smoking and the relationship between metabolic risk-factor burden and HCC (p=0.0044 for interaction) or liver-related death (p=0.0015 for interaction).

Indeed, among smokers, the 10-year cumulative incidence of HCC was 25.0% in those with three or more metabolic risk factors compared with 3.9% in those with no metabolic risk factors (p<0.0001), resulting in an adjusted HR of 5.06.

By contrast, having at least three metabolic risk factors did not increase HCC risk among never smokers, at a hazard ratio of 0.43 and 10-year cumulative incidence rates of 3.6% and 5.2%, respectively.

Yu and team also found that the effect of high metabolic risk factor burden on HCC was more pronounced among patients with low HBV viral load (<10,000 copies/mL) than among those with high viral load (≥10,000 copies/mL), at HRs of 14.38 and 6.65, respectively, for three or more versus no metabolic risk factors.

“Thus, despite the majority of HBV-related HCC cases accounted for by high viral load our data suggest that there exists some cases of HBV-related HCC arising in the background of metabolic syndrome, which represents a distinct clinicopathologic entity that has not yet achieved adequate attention in clinical practice and disease prevention,” they say.

“If our findings are confirmed, then the results of this study suggest that a substantial fraction of HBV-related HCC cases, especially those with low viral loads, might be prevented by management of metabolic risk factors and cessation of smoking,” Yu et al conclude.